Stephen Friend: The hunt for "unexpected genetic heroes"

Prevodilac: Jovana Zorić Lektor: Mile Živković

Approximately 30 years ago,

Pre otprilike 30 godina,

when I was in oncology at the Children's Hospital

dok sam bio na onkologiji u Dečjoj bolnici

in Philadelphia,

u Filadelfiji,

a father and a son walked into my office

u moju kancelariju ušli su otac i sin

and they both had their right eye missing,

i obojica nisu imali desno oko.

and as I took the history, it became apparent

Iz istorije bolesti postalo mi je jasno

that the father and the son had a rare form

da su otac i sin imali redak oblik

of inherited eye tumor, retinoblastoma,

naslednog tumora oka, retinoblastom,

and the father knew that he had passed that fate

i otac je znao da je preneo bolest

on to his son.

svome sinu.

That moment changed my life.

Taj trenutak mi je promenio život.

It propelled me to go on

Motivisao me je da nastavim

and to co-lead a team that discovered

i povedem tim koji je otkrio

the first cancer susceptibility gene,

prvi gen koji je prijemčiv na rak.

and in the intervening decades since then,

U proteklim decenijama

there has been literally a seismic shift

desio se seizmički preokret

in our understanding of what goes on,

u našem poimanju onoga što se dešava,

what genetic variations are sitting behind

kakve se to genetske varijacije kriju iza

various diseases.

raznih bolesti.

In fact, for thousands of human traits,

Zapravo, za hiljade ljudskih osobina,

a molecular basis that's known for that,

molekularna osnova koja stoji iza toga

and for thousands of people, every day,

i za hiljade ljudi, svakodnevno

there's information that they gain

postoje informacije koje dobijaju

about the risk of going on to get this disease

o riziku da obole od ove

or that disease.

ili one bolesti.

At the same time, if you ask,

Istovremeno, ako se zapitate:

"Has that impacted the efficiency,

"Da li je to uticalo na efikasnost,

how we've been able to develop drugs?"

na našu sposobnost pravljenja lekova?"

the answer is not really.

Odgovor je: ne baš.

If you look at the cost of developing drugs,

Ako pogledate troškove pravljenja lekova,

how that's done, it basically hasn't budged that.

u osnovi se nije ništa promenilo.

And so it's as if we have the power to diagnose

Tako da imamo moć da dijagnostikujemo,

yet not the power to fully treat.

ali ne i moć da izlečimo.

And there are two commonly given reasons

A postoje dva razloga koji se navode

for why that happens.

za to zašto se ovo dešava.

One of them is it's early days.

Jedan od njih je da tek počinjemo.

We're just learning the words, the fragments,

Tek učimo reči, fragmente,

the letters in the genetic code.

slova u genetskom kodu.

We don't know how to read the sentences.

Ne umemo da čitamo rečenice.

We don't know how to follow the narrative.

Ne umemo da pratimo priču.

The other reason given is that

Drugi navedeni razlog je da je

most of those changes are a loss of function,

većina ovih promena gubitak funkcije,

and it's actually really hard to develop drugs

a veoma je teško stvoriti lekove

that restore function.

koji vraćaju funkciju.

But today, I want us to step back

Ali danas želim da se vratimo korak unazad

and ask a more fundamental question,

i upitamo se jedno osnovnije pitanje:

and ask, "What happens if we're thinking

"Šta se dešava ako ovo posmatramo

about this maybe in the wrong context?"

možda u pogrešnom kontekstu?"

We do a lot of studying of those who are sick

Mnogo proučavamo one koji su bolesni

and building up long lists

i pravimo duge spiskove

of altered components.

izmenjenih komponenti.

But maybe, if what we're trying to do

Ali možda, ako pokušavamo da

is to develop therapies for prevention,

napravimo terapiju za prevenciju,

maybe what we should be doing

možda bi trebalo

is studying those who don't get sick.

da proučavamo one koji se ne razbole.

Maybe we should be studying those

Možda bi trebalo da proučavamo one

that are well.

koji su zdravi.

A vast majority of those people

Velika većina tih ljudi

are not necessarily carrying a particular

ne nosi nužno neko posebno

genetic load or risk factor.

genetsko opterećenje ili faktor rizika.

They're not going to help us.

Oni nam neće pomoći.

There are going to be those individuals

To će biti oni pojedinci

who are carrying a potential future risk,

koji nose potencijalni budući rizik,

they're going to go on to get some symptom.

oni će ispoljiti neki simptom.

That's not what we're looking for.

To nije ono što tražimo.

What we're asking and looking for is,

Ono što mi želimo i tražimo

are there a very few set of individuals

je mali broj pojedinaca

who are actually walking around

koji zapravo žive

with the risk that normally would cause a disease,

sa rizikom koji bi normalno izazvao bolest,

but something in them, something hidden in them

ali ih nešto u njima, nešto skriveno,

is actually protective

u stvari štiti

and keeping them from exhibiting those symptoms?

i sprečava te simptome da se ispolje.

If you're going to do a study like that, you can imagine

U takvom istraživanju, možete da zamislite,

you'd like to look at lots and lots of people.

treba da pregledate zaista mnogo ljudi.

We'd have to go and have a pretty wide study,

Trebalo bi da sprovedemo prilično široko istraživanje

and we realized that actually

i shvatili smo da je

one way to think of this is,

jedan od načina da pristupimo ovome

let us look at adults who are over 40 years of age,

da uzmemo odrasle ljude iznad 40 godina starosti

and let's make sure that we look at those

i da se pobrinemo da to budu oni

who were healthy as kids.

koji su bili zdravi u detinjstvu.

They might have had individuals in their families

Moguće je da su imali članove porodice

who had had a childhood disease,

koji su bili bolesni u detinjstvu,

but not necessarily.

ali to nije nužno.

And let's go and then screen those

I hajde da na njima uradimo skrining

to find those who are carrying genes

kako bismo pronašli one koji nose gene

for childhood diseases.

za dečje bolesti.

Now, some of you, I can see you

E sad, mogu da vidim neke od vas

putting your hands up going, "Uh, a little odd.

kako podižete ruke u stilu: "Ovaj, pomalo čudno.

What's your evidence

Šta dokazuje

that this could be feasible?"

da je ovo izvodljivo?"

I want to give you two examples.

Želim da vam dam dva primera.

The first comes from San Francisco.

Prvi dolazi iz San Franciska.

It comes from the 1980s and the 1990s,

Dolazi iz 1980-ih i 1990-ih,

and you may know the story where

a možda vam je poznata priča

there were individuals who had very high levels

o pojedincima koji su imali vrlo visoke nivoe

of the virus HIV.

virusa HIV.

They went on to get AIDS.

Oni su dobili sidu.

But there was a very small set of individuals

Ali postojao je mali broj ljudi

who also had very high levels of HIV.

koji su isto imali visok nivo HIV-a.

They didn't get AIDS.

Oni nisu oboleli od side.

And astute clinicians tracked that down,

Pronicljivi lekari su ovo istražili

and what they found was they were carrying mutations.

i otkrili da su ti ljudi nosioci mutacija.

Notice, they were carrying mutations from birth

Obratite pažnju da su one tu od rođenja.

that were protective, that were protecting them

Mutacije su služile kao zaštita

from going on to get AIDS.

od dobijanja side.

You may also know that actually a line of therapy

Možda vam je poznato da su razne terapije

has been coming along based on that fact.

nastale upravo na osnovu tog saznanja.

Second example, more recent, is elegant work

Drugi, noviji, primer je elegantno delo

done by Helen Hobbs,

Helen Hobs

who said, "I'm going to look at individuals

koja je rekla: "Pregledaću pojedince

who have very high lipid levels,

koji imaju visok nivo lipida

and I'm going to try to find those people

i pokušaću da nađem one ljude

with high lipid levels

sa visokim nivoom lipida

who don't go on to get heart disease."

koji ne dobiju srčano oboljenje."

And again, what she found was

I opet, otkrila je

some of those individuals had mutations

da neki od tih pojedinaca imaju mutacije

that were protective from birth that kept them,

koje su ih štitile od rođenja

even though they had high lipid levels,

uprkos visokom nivou lipida.

and you can see this is an interesting way

Možete da vidite da je ovo zanimljiv način

of thinking about how you could develop

razmišljanja o tome kako napraviti

preventive therapies.

preventivnu terapiju.

The project that we're working on

Projekat na kome radimo

is called "The Resilience Project:

zove se "Projekat otpornosti:

Potraga za neočekivanim herojima",

A Search for Unexpected Heroes,"

because what we are interested in doing is saying,

jer želimo da otkrijemo

can we find those rare individuals

da li možemo da nađemo one retke pojedince

who might have these hidden protective factors?

koji imaju ove skrivene zaštitne faktore.

And in some ways, think of it as a decoder ring,

Posmatrajte to kao krug dešifrovanja,

a sort of resilience decoder ring

nekakav krug dešifrovanja za otpornost

that we're going to try to build.

koji želimo da izgradimo.

We've realized that we should do this in a systematic way,

Shvatamo da ovo treba uraditi sistematično,

so we've said, let's take every single

tako da smo odlučili da uzmemo svaku moguću

childhood inherited disease.

naslednu dečju bolest.

Let's take them all, and let's pull them back a little bit

Hajde sve da ih uzmemo i malo izuzmemo

by those that are known to have severe symptoms,

one koji imaju teške simptome,

where the parents, the child,

gde roditelji, dete,

those around them would know

oni oko njih znaju

that they'd gotten sick,

da su se razboleli.

and let's go ahead and then frame them again

I hajde da ponovo uzmemo te bolesti

by those parts of the genes where we know

i posmatramo one delove gena za koje znamo

that there is a particular alteration

da imaju neku posebnu promenu

that is known to be highly penetrant

za koju se zna da je veoma prodorna

to cause that disease.

u izazivanju te bolesti.

Where are we going to look?

Gde ćemo gledati?

Well, we could look locally. That makes sense.

Pa, mogli bismo lokalno. To ima smisla.

But we began to think, maybe we should look

Ali palo nam je na pamet, možda treba

all over the world.

da gledamo širom sveta.

Maybe we should look not just here

Možda ne treba da gledamo samo ovde

but in remote places where their might be

nego u udaljenim mestima gde možda postoji

a distinct genetic context,

poseban genetski kontekst,

there might be environmental factors

možda postoje faktori sredine

that protect people.

koji štite ljude.

And let's look at a million individuals.

I hajde da pregledamo milion pojedinaca.

Now the reason why we think it's a good time

A razlog zašto mislimo da je pravo vreme

to do that now

da to uradimo sada

is, in the last couple of years,

je činjenica da se u poslednjih par godina

there's been a remarkable plummeting in the cost

desio neverovatan pad troškova

to do this type of analysis,

ovakvog tipa analize,

this type of data generation,

ovakvog tipa izdvajanja podataka

to where it actually costs less to do

gde zapravo manje košta

the data generation and analysis

izdvajanje i analiza podataka

than it does to do the sample processing and the collection.

nego obrada i prikupljanje uzoraka.

The other reason is that in the last five years,

Drugi razlog je to što su se u poslednjih

there have been awesome tools,

pet godina pojavili sjajni alati,

things about network biology, systems biology,

stvari u vezi sa mrežnom i sistemskom biologijom

that have come up that allow us to think

koje su se pojavile i navele nas da pomislimo

that maybe we could decipher

da možda možemo da odgonetnemo

those positive outliers.

te pozitivne izuzetke.

And as we went around talking to researchers

I kako smo počeli da pričamo sa naučnicima

and institutions

i institucijama

and telling them about our story,

i ispričali im našu priču,

something happened.

nešto se desilo.

They started saying, "This is interesting.

Govorili su nam: "To je zanimljivo.

I would be glad to join your effort.

Rado bismo se priključili vašem naporu.

I would be willing to participate."

Rado bismo učestvovali."

And they didn't say, "Where's the MTA?"

Nisu rekli: "Gde je sporazum o transferu materijala?"

They didn't say, "Where is my authorship?"

Nisu rekli: "Gde je moje autorstvo?"

They didn't say, "Is this data going to be mine? Am I going to own it?"

Nisu rekli: "Hoće li podaci biti moje vlasništvo?"

They basically said, "Let's work on this

Samo su rekli: "Hajde da radimo na ovome

in an open, crowd-sourced, team way

otvoreno, zajednički i timski

to do this decoding."

kako bismo uspeli u dekodiranju."

Six months ago, we locked down

Pre šest meseci, utvrdili smo

the screening key for this decoder.

skrining ključ za ovaj dekoder.

My co-lead, a brilliant scientist, Eric Schadt

Moj saradnik, briljantni naučnik, Erik Šat

at the Icahn Mount Sinai School of Medicine in New York,

sa Medicinskog fakulteta Ajkan Maunt u Njujorku

and his team,

i njegov tim,

locked in that decoder key ring,

otkrili su taj ključ za dekodiranje.

and we began looking for samples,

A mi smo počeli da tražimo uzorke

because what we realized is,

jer smo shvatili

maybe we could just go and look

da možda možemo da odemo i potražimo

at some existing samples to get some sense of feasibility.

postojeće uzorke i vidimo koliko je sve to izvodljivo.

Maybe we could take two, three percent of the project on,

Možda bismo mogli da uradimo 2-3% projekta

and see if it was there.

i vidimo kako ide.

And so we started asking people

Tako smo počeli da pitamo ljude

such as Hakon at the Children's Hospital in Philadelphia.

kao što su Haken iz Dečje bolnice u Filadelfiji.

We asked Leif up in Finland.

Pitali smo Lejfa iz Finske.

We talked to Anne Wojcicki at 23andMe,

Razgovarali smo sa En Vodžiki iz 23andMe

and Wang Jun at BGI,

i sa Vong Džun sa PGI-a.

and again, something remarkable happened.

I ponovo se desilo nešto neverovatno.

They said, "Huh,

Rekli su nam:

not only do we have samples,

"Ne samo da imamo uzorke,

but often we've analyzed them,

nego smo ih neretko i analizirali

and we would be glad to go into

i rado ćemo pregledati

our anonymized samples

naše anonimne uzorke

and see if we could find those

i probati da nađemo one

that you're looking for."

koji vam trebaju."

And instead of being 20,000 or 30,000,

I umesto da ih je 20 ili 30 hiljada,

last month we passed one half million samples

prošlog meseca prešli smo pola miliona uzoraka

that we've already analyzed.

koje smo već analizirali.

So you must be going,

Mora da se pitate:

"Huh, did you find any unexpected heroes?"

"Da li ste našli nekog neočekivanog heroja?"

And the answer is, we didn't find one or two.

A nismo pronašli jednog ili dva,

We found dozens of these strong candidate

već desetine jakih kandidata

unexpected heroes.

za neočekivane heroje.

So we think that the time is now

Tako da mislimo da je sad pravi trenutak

to launch the beta phase of this project

da izbacimo beta verziju ovog projekta

and actually start getting prospective individuals.

i zaista počnemo sa mogućim kandidatima.

Basically all we need is information.

Sve što nama u stvari treba je informacija.

We need a swab of DNA

Treba nam uzorak DNK

and a willingness to say, "What's inside me?

i želja da saznaju: "Šta se to nalazi u meni?

I'm willing to be re-contacted."

Hteo bih da mi se ponovo javite."

Most of us spend our lives,

Većina nas provodi život,

when it comes to health and disease,

kad govorimo o zdravlju i bolestima,

acting as if we're voyeurs.

u ulozi posmatrača.

We delegate the responsibility

Prepuštamo odgovornost

for the understanding of our disease,

razumevanja naših bolesti

for the treatment of our disease,

i lečenja naših bolesti

to anointed experts.

bogom danim stručnjacima.

In order for us to get this project to work,

Da bi ovaj projekat uspeo,

we need individuals to step up

pojedinci treba da se pokažu

in a different role and to be engaged,

u drugačijoj ulozi i da se uključe

to realize this dream,

kako bi se ostvario ovaj san,

this open crowd-sourced project,

ovaj otvoreni, zajednički projekat,

to find those unexpected heroes,

kako bi se pronašli ti neočekivani heroji

to evolve from the current concepts

i napredovalo sa sadašnjih ideja

of resources and constraints,

o resursima i ograničenjima,

to design those preventive therapies,

kako bi se osmislila preventivna terapija

and to extend it beyond childhood diseases,

i proširila van granica dečjih bolesti

to go all the way up to ways

tako da se smisle načini

that we could look at Alzheimer's or Parkinson's,

posmatranja Alchajmerove ili Parkinsonove bolesti.

we're going to need us

Trebaćemo sami sebi

to be looking inside ourselves and asking,

da se zagledamo u sebe i zapitamo:

"What are our roles?

"Koje su naše uloge?

What are our genes?"

Kakvi su naši geni?"

and looking within ourselves for information

Unutar sebe da tražimo informacije

we used to say we should go to the outside,

koje smo pre tražili spolja,

to experts,

od stručnjaka.

and to be willing to share that with others.

I da budemo spremni da to podelimo sa drugima.

Thank you very much.

Mnogo vam hvala.

(Applause)

(Aplauz)